Every year, a committee of experts sits down with a tough job to do: from among all ICREA publications, they must find a handful that stand out from all the others. This is indeed a challenge. The debates are sometimes heated and always difficult but, in the end, a shortlist of 24 publications is produced. No prize is awarded, and the only additional acknowledge is the honour of being chosen and highlighted by ICREA. Each piece has something unique about it, whether it be a particularly elegant solution, the huge impact it has in the media or the sheer fascination it generates as a truly new idea. For whatever the reason, these are the best of the best and, as such, we are proud to share them here.


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  • 'Human Epidermal Stem Cell Function Is Regulated by Circadian' (2013)

    Aznar Benitah, Salvador (IRB Barcelona)

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    'Human Epidermal Stem Cell Function Is Regulated by Circadian'

    Human skin copes with harmful environmental factors that are circadian in nature, yet how circadian rhythms modulate the function of human epidermal stem cells is mostly unknown. In this paper we show that in human epidermal stem cells and their differentiated counterparts, core clock genes peak in a successive and phased manner, establishing distinct temporal intervals during the 24hr day period. Each of these successive clock waves is associated with a peak in the expression of subsets of transcripts that temporally segregate the predisposition of epidermal stem cells to respond to cues that regulate their proliferation or differentiation, such as TGFβ and calcium. Accordingly, circadian arrhythmia profoundly affects stem cell function in culture and in vivo. We hypothesize that this intricate mechanism ensures homeostasis by providing epidermal stem cells with environmentally-relevant temporal functional cues during the course of the day, and that its perturbation may contribute to ageing and to carcinogenesis.

  • Is multiculturalism psychologically adaptive? (2013)

    Benet-Martínez, Verónica (UPF)

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    Is multiculturalism psychologically adaptive?

    Intercultural contact has a long history due to migration, transnationalism, or colonization, and more recently also due to cultural and economic globalization forces, and the speed of travel and communication. One result of this intercultural contact and mixing is the growing numbers of individuals who consider themselves bicultural or multicultural. Early sociological accounts of this phenomenon portrayed bicultural individuals as marginal and stumped between two worlds, and more recently, in the context of immigration, political discourse supportive of assimilation (i.e., abandoning the culture of origin in favor of the dominant culture) has become quite pervasive. But one question remains: What are the consequences of these intercultural and identity processes for individuals’ psychological, sociocultural, and health-related adjustment? To answer this question, we conducted a statistical meta-analysis that pooled data from 83 international studies, 322 effect sizes, and 23,197 acculturating participants (e.g., immigrants, ethnic and cultural minorities, international students). Results showed a strong and positive association between biculturalism –i.e., attachment to and competency in two cultures-- and both psychological (e.g., self-esteem, lack of depression) and sociocultural (e.g., career success, lack of delinquency) adjustment. This link between biculturalism and adjustment was stronger than the association between monoculturalism (exclusive orientation towards either the dominant or heritage/ethnic cultures) and adjustment. These results thus clearly invalidate both early sociological accounts of this phenomenon depicting bicultural individuals as “lost” between two worlds and also political discourse supportive of either assimilation or ethnic segregation. The positive relationship between biculturalism and adjustment may be due to a variety of factors internal and external to the acculturating individual. For instance, the cultural, linguistic, social, and cognitive competencies that bicultural individuals acquire in the process of learning and using two cultures may make these individuals more adept at adjusting to various life situations (i.e., have higher adjustment). Also, having social support networks in two cultures may buffer biculturals from the psychological and sociocultural challenges that sometimes result from acculturation experiences. Alternatively, perhaps better adjusted individuals find it easier to be bicultural. Lastly, societies supportive of multicultural

  • Investigating ancient wine residues in archaeological materials (2013)

    Cau Ontiveros, Miguel Ángel (UB)

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    Investigating ancient wine residues in archaeological materials

    Wine is one of the most important products produced, traded and consumed in the Mediterranean area in Antiquity. Consequently, its identification in archaeological materials provides valuable information in order to understand food production, trade and consumption. Investigation of organic residues in archaeological materials has been developed since the decade of 1970. Ceramics (Figure 1) and other porous materials such as plasters retain the substances in which they enter in contact with. Gas chromatography/mass spectrometry (GC/MS) is one of the methods most widely used for the identification of organic residues. Nevertheless, the identification of wine markers has always been difficult due to the problems of degradation. A new extraction method for the identification of tartaric acid and other markers of wine and its derivatives is proposed. Although tartaric acid is soluble in water, when it is identified, it can be considered a marker of wine or its derivatives. The results obtained with this extraction method and using gas chromatography/mass spectrometry (GC/MS), allowed for the identification of tartaric acid and other markers of wine. The method was tested on experimental, traditional materials used to store and/or produce wine, and finally applied to the study of archaeological materials (ceramics and plasters). The experiments also involved the degradation of wine through cooking, drastic heating and burial. The importance of the proposed methodology is that it allows the identification of traces of wine using the same facilities that are usually employed for the study of the organic residues preserved in archaeological samples (GC/MS), with no need for HPLC, LC/MS/MS or THM/GC/MS, thus allowing a larger number of laboratories to detect traces of wine. This will allow laboratories that only have a GC/MS to use a single instrument for the identification of lipids and wine markers, providing a deeper understanding of the residues preserved in the samples. This is particularly important in the case of archaeological samples, as they often come in contact with different substances. Amphorae as the most widely distributed container were often re-used. These results published in the Journal of Archaeological Science (Figure 2) are part of a larger project on production, trade and consumption of food in Late Antiquity that explores food practices in this period of deep transformation of the Mediterranean world between the Roman

  • Mucus enhances gut homeostasis and oral tolerance by delivering tolerogenic signals (2013)

    Cerutti, Andrea (IMIM)

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    Mucus enhances gut homeostasis and oral tolerance by delivering tolerogenic signals

    The gastrointestinal tract is home to the highest density of commensal bacteria in the human body and is a primary site of pathogen exposure. Understanding how the immune system recognizes and responds to friend or foe in the gut is central to developing treatments for allergic and inflammatory diseases. A mucus layer covers the entire gastrointestinal tract, physically separating the microbiota from host tissue and preventing pathogen invasion. We now show that mucus does more than act as a shield—it also influences the function of intestinal antigen-presenting cells and epithelial cells to sustain the ability of the host to maintain tolerance toward food and commensal antigens. We found that the gut mucus educates dendritic cells (DCs) to develop tolerance toward food and commensal antigens. DCs lie beneath the intestinal epithelial cell layer and present antigens to other cells of the immune system. Exposure of DCs to mucin-2 (MUC2), a major mucus component, subdues their responses to microbe-derived signals and also promotes their capacity to stimulate the production of regulatory T cells (Tregs), key determinants of oral tolerance. In particular, we observed that MUC2 increased the expression of factors by DCs that allow them to induce Treg production such as transforming growth factor–β (TGF-β) and retinaldehyde dehydrogenase, an enzyme involved in generating retinoic acid. Moreover, MUC2 also acted directly on epithelial cells to stimulate their release of molecules that support DC regulatory function. The ability of MUC2 to promote regulatory responses depends on the interaction of glycan moieties present on MUC2 with galectin-3 (a carbohydrate-binding protein) and the capacity of this complex to engage Dectin-1 on the surface of DCs. The downstream effect of Dectin-1 interaction with MUC-2 is the expression of β-catenin, a factor that can control the tolerogenic function of gut DCs. These results imply that by amplifying various aspects of the gut regulatory network, mucus may be a central determinant of gut immune specification and immune tolerance. Our findings are of particular relevance to understanding severe inflammatory conditions such as inflammatory bowel diseases. Changes to mucus glycosylation can occur during inflammatory responses, and altered glycosylation of mucus has been associated with colitis. Because of the physical protection afforded by mucus, strategies that restore its integrity in inflammatory diseases a

  • The connectivity between motor and auditory areas mediates word learning abilities (2013)

    de Diego Balaguer, Ruth (UB)
    Rodríguez Fornells, Antoni (UB)

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    The connectivity between motor and auditory areas mediates word learning abilities

    Humans are endowed with an amazing capacity to learn words throughout the lifespan. However great individual differences characterise the word learning abilities. This differences may rely on the integration between auditory and motor information that allow the translation of the linguistic auditory information into articulatory gestures. We combined diffusion imaging tractography to dissect the fiber tracts connecting auditory and motor brain areas and functional magnetic resonance imaging to study whether the strength of anatomical and functional connectivity between auditory and motor language networks is associated with word learning ability. We showed that performance in word learning correlates with microstructural properties and strength of functional connectivity of the direct connections between Broca’s and Wernicke’s territories in the left hemisphere. The participants were scanned while listening to an artificial language made of a fluent speech built with nine trisyllabic words that were randomly repeated during four minutes. Word recognition of these words was tested immediately after language learning. The study suggests that our ability to learn new words relies on an efficient and fast communication between temporal and frontal areas responsible of auditory and motor processing respectively. The results of this study may have also implications in evolutionary terms. The absence of these connections in other animals may explain the unique ability of learning words in humans.

  • Biosensing of individual molecules: Catching one within millions with optical antennas inside nano-boxes. (2013)

    García Parajo, Maria F. (ICFO)

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    Biosensing of individual molecules: Catching one within millions with optical antennas inside nano-boxes.

    A single cell in our body is composed by thousands of millions of different biomolecules that work together in an extreme coordinated manner. Likewise, many biological and biochemical reactions occur only if molecules are present at very high concentrations. Understanding how all these molecules interact with each other is key to advance our knowledge in molecular and cell biology. Unfortunately, detecting one molecule within millions of other neighbouring molecules has been technically impossible until now.  The key to succeed relies on foreseeing a device that shrinks the observation region to a tiny size that is comparable to the size of the molecule itself, that is, only a few nanometres. Together with the Fresnel Institute in Marseille we have conceived and fabricated the smallest optical device that can detect and sense individual biomolecules at concentrations that are similar to those found in the cellular context. The device called “antenna-in-a-box” consists on a tiny dimer antenna made out of two gold semi-spheres and separated from each other by a gap as small as 15nm. Light sent to this antenna is enormously amplified in the gap region where the actual detection of the biomolecule of interest occurs. Because amplification of the light is confined to the dimensions of the gap, only molecules present in this tiny region are detected. As additional trick, we embed the dimer antennas inside boxes also of nanometric dimensions. The box screens out the unwanted contribution of millions of other surrounding molecules, reducing the background and improving as a whole the detection of individual biomolecules. When tested under different sample concentrations, this novel antenna-in-box device allowed for 1100-fold fluorescence brightness enhancement together with detection volumes down to 58 zeptoliters (1 zL = 10-21L), i.e., the smallest observation volume in the world. Our antenna-in-box offers a highly efficient platform for performing a multitude of nanoscale biochemical assays with single molecule sensitivity at physiological conditions. It could be used for ultrasensitive sensing of minute amount of molecules, becoming an exquisite early diagnosis device for biosensing of many disease markers.  It could be also used as an ultra-bright optical nanosource to lighten up molecular processes in living cells and ultimately watch how individual biomolecules interact with each other, a long awaited dream of biologists.